ENERGETICS OF QUASIEQUIVALENCE - COMPUTATIONAL ANALYSIS OF PROTEIN-PROTEIN INTERACTIONS IN ICOSAHEDRAL VIRUSES

Quaternary structure polymorphism found in quasiequivalent virus capsi ds provides a static framework for studying the dynamics of protein in teractions. The same protein subunits are found in different structura l environments within these particles, and in some cases, the molecula r switching required for the polymorphic quaternary interactions is ob vious from high-resolution crystallographic studies. Employing atomic resolution structures, molecular mechanics, and continuum electrostati c methods, we have computed association energies for unique subunit in terfaces of three icosahedral viruses, black beetle virus, southern be an virus, and human rhinovirus 14. To quantify the chemical determinan ts of quasiequivalence, the energetic contributions of individual resi dues forming quasiequivalent interfaces were calculated and compared, The potential significance of the differences in stabilities at quasie quivalent interfaces was then explored with the combinatorial assembly approach. The analysis shows that the unique association energies com puted for each virus serve as a sensitive basis set that may determine distinct intermediates and pathways of virus capsid assembly. The pat hways for the quasiequivalent viruses displayed isoenergetic oligomers at specific points, suggesting that these may determine the quaternar y structure polymorphism required for the assembly of a quasiequivalen t particle.